Abstract
Dendritic cell (DC) function is negatively affected by tumors and tumor-derived factors, but little is known about the underlying mechanisms. Here, we show that intracellular SOCS3 in DCs binds to pyruvate kinase type M2 (M2-PK), which plays a critical role in ATP production through glycolysis. The interaction of SOCS3 with M2-PK reduced ATP production and impaired DC-based immunotherapy against tumors. Thus, SOCS3, which has been shown to be upregulated by tumor-derived factors, interacts with M2-PK to decrease ATP production, causing DC dysfunction. These dysfunctional DCs have a reduced ability to present antigens. Alteration of DC metabolism mediated by SOCS3 represents a novel mechanism for DC dysfunction in the tumor microenvironment.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphate / biosynthesis
-
Animals
-
Antigen Presentation / immunology*
-
Blotting, Western
-
Dendritic Cells / immunology
-
Dendritic Cells / metabolism*
-
Dendritic Cells / transplantation
-
Immunoprecipitation
-
Immunotherapy
-
LLC-PK1 Cells
-
Male
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Neoplasms, Experimental / immunology
-
Neoplasms, Experimental / therapy
-
Pyruvate Kinase / immunology
-
Pyruvate Kinase / metabolism*
-
Reverse Transcriptase Polymerase Chain Reaction
-
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
-
Suppressor of Cytokine Signaling 3 Protein
-
Suppressor of Cytokine Signaling Proteins / immunology
-
Suppressor of Cytokine Signaling Proteins / metabolism*
-
Swine
Substances
-
Socs3 protein, mouse
-
Suppressor of Cytokine Signaling 3 Protein
-
Suppressor of Cytokine Signaling Proteins
-
Adenosine Triphosphate
-
Pyruvate Kinase